Physical exercise can have significant effects on numerous growth and metabolic processes in skeletal muscle. A single bout of exercise can later rates of skeletal muscle glucose uptake, glycogen metabolism, gene transcription and protein synthesis. Although exercise is a critical regulator of so many cellular processes, little is known about the molecular signaling events that mediate these important physiological responses. In deed, despite a wealth of literature over the last several years characterizing the molecular details of several intracellular signaling pathways in cultured cells, little of this information has been incorporated into understanding the molecular basis for the clinically-important adaptations that occur in skeletal muscle in response to exercise. The overall goal of this research project is to determine the underlying molecular signaling mechanisms through which physical exercise regulates growth and metabolism in rat skeletal muscle. Studies are designed to investigate the specific mechanisms through which exercise increases glucose transport, glycogen synthesis, and gene transcription in skeletal muscle. To achieve these goals, some experiments will investigate 3 intracellular signaling pathways (MAP kinase, JNK, p38 that have been shown to be activated by exercise. Experiments are designed to determine the physiological consequences of the exercise-induced activation of these signaling cascades, and to define the "upstream" mechanisms that lead to the stimulation of these pathways by exercise. Additional studies will investigate the regulation of exercise-stimulated glucose transport by studying the subcellular distribution and physical association of signaling proteins with the glucose transport system Furthermore, as this work progresses, other novel signaling pathways and molecules will be investigated that may eventually prove to be critical in regulating the numerous biological effects of exercise in skeletal muscle. These studies will continue to define the molecular mechanisms of exercise-stimulated changes in skeletal muscle growth and metabolism. Ultimately, these studies should provide us with a better understanding of how regular physical exercise exerts salutary effects on human diseases.